Our ultimate goal is to develop a serological marker that can provide an early indication of response to therapy in resected melanoma. There is a critical need for such a marker, as presently the only way to judge response to adjuvant therapy is to wait for disease recurrence. By that time, the best chance to treat the cancer may have been lost. We will investigate whether serum levels of CYT-MAA, an antigen associated with melanoma, can provide this information. The proposal is based on very promising pilot data indicating CYT-MAA is present in serum of many patients with resected melanoma, that adjuvant therapy can decrease serum levels of this antigen, and that this is associated with an improved clinical outcome. In the R21 phase, we will: 1) Optimize and 2) validate a sensitive and quantitative sandwich ELISA we have developed to measure serum CYT-MAA. In the R33 phase, we will apply the optimized assay to formally examine its value as a prognostic marker of melanoma and as an early marker of response to therapy. The questions to be addressed include: 1) The incidence and level of serum CYT-MAA in patients with different stages of resected melanoma and age- matched individuals without melanoma. 2) The correlation between presence and/or level of this marker and clinical outcome. 3) The changes that occur in serum levels of CYT-MAA with treatment in patients with resected melanoma and whether these correlate with clinical outcome. 4) Whether serum CYT-MAA provides an earlier or more useful indication of response to therapy than other markers such as LDH and S100B. The strengths of the proposal are: a) It addresses a serious unmet need in the care of melanoma, b) pilot data indicates CYT-MAA appears to be a sensitive marker of early response to therapy, c) access to large sera banks containing specimens collected serially during therapy of melanoma with a variety of agents together with linked clinical outcome data, d) multi-institutional collaborations between very experienced investigators with complementary experience in the skills required to conduct this work. Successful completion of this work will provide a surrogate marker of disease progression and/or response to therapy in resected melanoma that will improve clinical decision making by permitting more rapid identification of unresponsive patients who would benefit from early introduction of alternate therapy. [unreadable] [unreadable] [unreadable]